Back to resultsFirst in Human Study of the Infusion of ARI0003 Cells in Relapsed/Refractory to Treatment B-cell Aggressive Lymphoma (CARTD-BG-1)
Primary Purpose
Refractory Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma
Status
Not yet recruiting
Phase
Early Phase 1
Locations
Spain
Study Type
Interventional
Intervention
ARI0003
Sponsored by
About this trial
This is an interventional treatment trial for Refractory Non-Hodgkin Lymphoma
Eligibility Criteria
Inclusion Criteria: 1. Diagnosis of CD19+ or CD269+ relapsed/refractory (R/R) aggressive B-cell lymphoma in one of the following circumstances: Burkitt's lymphoma; Histology not covered by approved CART19-cell products (plasmablastic lymphoma, primary effusion lymphoma, intravascular lymphoma, transformed lymphoma from marginal zone lymphoma or chronic lymphocytic leukaemia, primary cutaneous DLBCL, T-cell rich DLBCL, high-grade B-cell lymphoma, grey zone lymphoma or grade 3b follicular lymphoma); or Aggressive B-cell lymphoma that is refractory or relapsing after treatment with CART19-cell therapy. 2. Age older than 18 years. 3. ECOG performance status of 0-2. 4. Estimated life expectancy of at least 3 months. 5. Adequate venous access and absence of contraindications for lymphapheresis. 6. Signature of informed consent. 7. In patients who have received any anti-CD19 or anti-CD269 therapy (e.g. tisagenlecleucel, axicabtagene autoleucel, tafasitamab, loncastuximab, belantamab mafodotin, idecabtagene vicleucel, etc.), a centralised tumour sample confirming the expression of at least one of the antigens (either CD19 or CD269) will be needed at study inclusion Exclusion Criteria: 1. Any experimental or non-commercialized therapy in the previous 4 weeks. 2. Any other concomitant neoplasia, unless it has been in complete remission for 3 years or longer, except for non-melanoma skin cancer or completely resected in situ carcinoma. 3. Active immunosuppressive therapy except for prednisone 10 mg/day (or equivalent). 4. Active infection requiring systemic medical therapy. 5. Active HBV or HCV infection. 6. Positive serology for HIV. 7. Any concomitant and uncontrolled medical disease. 8. Severe organic impairment defined by cardiac ejection fraction <40%, DLCO <40%, GFR <30 ml/min or bilirubin >3 times the upper limit of normality (unless due to Gilbert's syndrome). 9. Lactating or pregnant women. 10. Men or women of childbearing potential unable or unwilling to use highly efficient contraceptive measures from the beginning until the end of the study. 11. CNS disease in the form of a macroscopic solid lesion in the encephalon or spinal cord (isolated meningeal disease is allowed
Sites / Locations
- CHU Santiago de Compostela
- Hospital Clínic Barcelona
- H. Ramon y Cajal
- H.U. Virgen de la Arrixaca
- Hospital Central de Asturias
- Hospital Son Espases
- H. Clínico de Salamanca
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ARI0003
Arm Description
ARI0003 will be administered intravenously under a split regime. A total dose between 0.5 and 5 x106 cell/Kg will be administered in 3 administrations (fractions):
Outcomes
Primary Outcome Measures
Rate of > grade 3 CRS and/or ICANS
Rate of patients who develop grade > 3 cytokine release syndrome (CRS) and/or grade > 3 immune cell associated neurotoxicity syndrome (ICANS) according to the criteria and grading defined in the international consensus document (ASTCT criteria)
ORR
Overall response rate (ORR) according to Lugano criteria (best response within 3 months post ARI0003 infusion
Secondary Outcome Measures
Procedure-related mortality (PRM)
Procedure-related mortality (PRM), defined as any death not directly cause by the lymphoma that is related with the procedure. For the estimation of PRM, disease relapse will be considered as a competing event
Toxicity: incidence of AE
Toxicity defined as the incidence of grade >3 adverse events (AEs) as per CTCAE version 5.0. The following AEs will be considered AEs of special interest (AESI): CRS, ICANS, macrophagic activation syndrome (MAS), tumour lysis syndrome (TLS), prolonged cytopenia (beyond 6 months), infections and second primary malignancies
Complete response rate
Complete response rate
Duration of response,
Duration of response, calculated from the time of first disease evaluation (3 months);
Progression-free survival
Progression-free survival, calculated from ARI-0003 cell infusion
Overall survival
Overall survival, calculated from ARI-0003 cell infusion
Full Information
NCT ID
NCT06097455
First Posted
October 9, 2023
Last Updated
October 18, 2023
Sponsor
Fundacion Clinic per a la Recerca Biomédica
1. Study Identification
Unique Protocol Identification Number
NCT06097455
Brief Title
First in Human Study of the Infusion of ARI0003 Cells in Relapsed/Refractory to Treatment B-cell Aggressive Lymphoma
Acronym
CARTD-BG-1
Official Title
First in Human, Pilot, Open-label, Prospective, Multicentre, Non-randomised Clinical Trial to Evaluate the Safety and Efficacy of ARI0003 (CART CD19/ CD269 Cells) in Patients With Relapsed/Refractory B-cell Aggressive Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 15, 2024 (Anticipated)
Primary Completion Date
April 15, 2025 (Anticipated)
Study Completion Date
January 15, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundacion Clinic per a la Recerca Biomédica
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
ths study consist in testing a CAR T therapy (ARI0003 cells (antiCD19 and antiBCMA) in patients suffering relapsed NHL (that means that symptoms of NHL reappeared ) or refractory (that means that they did not respond to other treatments). This is a first in human study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ARI0003
Arm Type
Experimental
Arm Description
ARI0003 will be administered intravenously under a split regime. A total dose between 0.5 and 5 x106 cell/Kg will be administered in 3 administrations (fractions):
Intervention Type
Genetic
Intervention Name(s)
ARI0003
Other Intervention Name(s)
Adult autologous differentiated T-cells from peripheral blood, expanded and co-transduced lentiviruses: one containing a chimeric antigen receptor anti-CD19 and another containing an anti-CD269 (BCMA)
Intervention Description
Treatment with ARI0003 cells
Primary Outcome Measure Information:
Title
Rate of > grade 3 CRS and/or ICANS
Description
Rate of patients who develop grade > 3 cytokine release syndrome (CRS) and/or grade > 3 immune cell associated neurotoxicity syndrome (ICANS) according to the criteria and grading defined in the international consensus document (ASTCT criteria)
Time Frame
in the first 30 days after ARI0003 administration
Title
ORR
Description
Overall response rate (ORR) according to Lugano criteria (best response within 3 months post ARI0003 infusion
Time Frame
within 3 months post ARI0003 infusion
Secondary Outcome Measure Information:
Title
Procedure-related mortality (PRM)
Description
Procedure-related mortality (PRM), defined as any death not directly cause by the lymphoma that is related with the procedure. For the estimation of PRM, disease relapse will be considered as a competing event
Time Frame
through study completion, an average of 24 months
Title
Toxicity: incidence of AE
Description
Toxicity defined as the incidence of grade >3 adverse events (AEs) as per CTCAE version 5.0. The following AEs will be considered AEs of special interest (AESI): CRS, ICANS, macrophagic activation syndrome (MAS), tumour lysis syndrome (TLS), prolonged cytopenia (beyond 6 months), infections and second primary malignancies
Time Frame
at 3 and 12 months
Title
Complete response rate
Description
Complete response rate
Time Frame
at 3 months
Title
Duration of response,
Description
Duration of response, calculated from the time of first disease evaluation (3 months);
Time Frame
from month 3 to study completion, an average of 24 months
Title
Progression-free survival
Description
Progression-free survival, calculated from ARI-0003 cell infusion
Time Frame
through study completion, an average of 24 months
Title
Overall survival
Description
Overall survival, calculated from ARI-0003 cell infusion
Time Frame
through study completion, an average of 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1. Diagnosis of CD19+ or CD269+ relapsed/refractory (R/R) aggressive B-cell lymphoma in one of the following circumstances:
Burkitt's lymphoma;
Histology not covered by approved CART19-cell products (plasmablastic lymphoma, primary effusion lymphoma, intravascular lymphoma, transformed lymphoma from marginal zone lymphoma or chronic lymphocytic leukaemia, primary cutaneous DLBCL, T-cell rich DLBCL, high-grade B-cell lymphoma, grey zone lymphoma or grade 3b follicular lymphoma); or
Aggressive B-cell lymphoma that is refractory or relapsing after treatment with CART19-cell therapy.
2. Age older than 18 years. 3. ECOG performance status of 0-2. 4. Estimated life expectancy of at least 3 months. 5. Adequate venous access and absence of contraindications for lymphapheresis. 6. Signature of informed consent. 7. In patients who have received any anti-CD19 or anti-CD269 therapy (e.g. tisagenlecleucel, axicabtagene autoleucel, tafasitamab, loncastuximab, belantamab mafodotin, idecabtagene vicleucel, etc.), a centralised tumour sample confirming the expression of at least one of the antigens (either CD19 or CD269) will be needed at study inclusion
Exclusion Criteria:
1. Any experimental or non-commercialized therapy in the previous 4 weeks. 2. Any other concomitant neoplasia, unless it has been in complete remission for 3 years or longer, except for non-melanoma skin cancer or completely resected in situ carcinoma.
3. Active immunosuppressive therapy except for prednisone 10 mg/day (or equivalent).
4. Active infection requiring systemic medical therapy. 5. Active HBV or HCV infection. 6. Positive serology for HIV. 7. Any concomitant and uncontrolled medical disease. 8. Severe organic impairment defined by cardiac ejection fraction <40%, DLCO <40%, GFR <30 ml/min or bilirubin >3 times the upper limit of normality (unless due to Gilbert's syndrome).
9. Lactating or pregnant women. 10. Men or women of childbearing potential unable or unwilling to use highly efficient contraceptive measures from the beginning until the end of the study.
11. CNS disease in the form of a macroscopic solid lesion in the encephalon or spinal cord (isolated meningeal disease is allowed
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Julio Delgado, MD PhD
Phone
+34932275400
Email
jdelgado@clinic.cat
First Name & Middle Initial & Last Name or Official Title & Degree
Sara Varea, MSc
Phone
+34932275400
Email
svarea@clinic.cat
Facility Information:
Facility Name
CHU Santiago de Compostela
City
Santiago De Compostela
State/Province
A Coruña
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adrián Mosquera Orgeira, MD
Facility Name
Hospital Clínic Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julio Delgado
Phone
+34932275400
Email
jdelgado@clinic.cat
Facility Name
H. Ramon y Cajal
City
Madrid
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Javier Lopez Jiménez, MD
Facility Name
H.U. Virgen de la Arrixaca
City
Murcia
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jose M Moraleda, MD PhD
Facility Name
Hospital Central de Asturias
City
Oviedo
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jose M Garcia Gala, MD
Facility Name
Hospital Son Espases
City
Palma De Mallorca
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leyre Bento de Miguel, MD
Facility Name
H. Clínico de Salamanca
City
Salamanca
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fermín Sanchez-Guijo
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
First in Human Study of the Infusion of ARI0003 Cells in Relapsed/Refractory to Treatment B-cell Aggressive Lymphoma
We'll reach out to this number within 24 hrs